Lume-lung 2: A multicenter, randomized, double-blind, phase III study of nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) after failure of first-line chemotherapy.

Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
Poster Discussion Session, Lung Cancer - Non-small Cell Metastatic
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 8034)
Nasser H. Hanna, Rolf Kaiser, Richard N. Sullivan, Osvaldo Rudy Aren, Myung-Ju Ahn, Beatrice Tiangco, Zanete Zvirbule, Carlos H. Barrios, Ahmet Demirkazik, Birgit Gaschler-Markefski, Isabelle Voccia, Jose Barrueco, Joo-Hang Kim; Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN; Boehringer Ingelheim GmbH, Biberach, Germany; Department of Oncology, Auckland City Hospital, Auckland, New Zealand; Instituto Nacional del Cancer, Santiago, Chile; Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Internal Medicine, National Kidney and Transplant Institute, Quezon City, Philippines; Department of Oncology, Rîga Eastern Clinical University Hospital, Riga, Latvia; Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil; Department of Medical Oncology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey; Boehringer Ingelheim (Canada) Ltd, Burlington, ON, Canada; Boehringer Ingelheim GmbH, Ridgefield, CT; Department of Internal Medicine (Medical Oncology), Yonsei Cancer Research Institute, Yonsei Cancer Center, Seoul, South Korea

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: Nintedanib (N) is an oral inhibitor of VEGFR, FGFR, and PDGFR. This global phase 3 study investigated the safety and efficacy of N + pemetrexed (PEM) vs placebo (P) + PEM in patients (pts) with advanced, non-squamous NSCLC previously treated with chemotherapy. Methods: Pts were randomized 1:1 to N 200 mg po bid + PEM 500 mg/m2 iv q21d (n=353, Arm A) or P + PEM (n=360, Arm B). Continuation until PD or unacceptable toxicity with N, P, PEM, or a combination was permitted. 1° endpoint was centrally reviewed PFS. The null hypothesis was tested on the ITT population after 394 events had occurred (two sided α=5%). 2° endpoints included OS, investigator-assessed PFS, response rate (RR), safety, and QoL. Results: Baseline pt characteristics were balanced between Arm A vs B (median age 59 y, female 45–42%, ECOG PS 1 62-61%, adenocarcinoma 95–93%, prior bevacizumab 8%). Based on a planned DMC futility analysis of investigator-assessed PFS, enrolment was halted after randomizing 713/1300 planned pts (no safety issues identified). Ongoing pts were unblinded and follow-up continued per protocol. Subsequent ITT analysis of the 1° endpoint (centrally reviewed PFS) favored Arm A vs B (median 4.4 vs 3.6 mo, HR 0.83 [95% CI: 0.7–0.99], p=0.04). Disease control was also significantly improved in N-treated pts (61 vs 53%, odds ratio 1.37, p=0.039). No difference in OS (HR 1.03) or RR (9%) was found. Exploratory analyses identified time since start of 1st-line therapy as a predictive marker of improved outcome with N + PEM (ASCO 2013). There was no increase in SAEs or G5 AEs with N + PEM. Addition of N to PEM resulted in a higher incidence of ≥G3 elevated ALT (23 vs 7%), elevated AST (12 vs 2%), and diarrhea (3 vs 1%), but no difference in ≥G3 hypertension, bleeding, thrombosis, mucositis, or neuropathy. Conclusions: The 1° endpoint was met even though the study was stopped prematurely. Treatment with N + PEM significantly improved centrally reviewed PFS vs P + PEM in pts with advanced non-squamous NSCLC previously treated with chemotherapy, and had a manageable safety profile. Clinical trial information: NCT00806819.